This final analysis includes an additional 5 months of treatment and follow up. There are now 91 PFS events out of 164 patients with baseline serum samples. The final analysis suggests that serum NRP1 may have both prognostic and predictive value. Serum NRP1 is associated with improved PFS and overall survival (OS) in multiple T studies in renal cell carcinoma (RCC). This strong association and clinical benefit in RCC prompted the inclusion of NRP-1 in the pre-specified biomarker panel.

Methods

Baseline serum from patients in BATON-CRC had serum biomarkers, including NRP1, quantified using the Myriad RBM ELISA assay. Per the statistical analysis plan, serum biomarkers were analyzed by comparing high and low using the median to define the cut point. A Cox proportional hazard model was used to assess the association between serum NRP1 levels and PFS.

Results

In BATON-CRC, 265 patients were enrolled and randomized 2:1 to T + mFOLFOX6 (n = 177) or B + mFOLFOX6 (n = 88). The updated ITT analysis is consistent with the interim analysis. The median PFS for the two arms are 9.8 for T and 9.5 months for B, with a HR of 0.908. The objective response rates were 46.9% for T and 43.2% for B.

A total of 164 baseline serum samples (T, n = 109 and B, n = 55) were available for NRP1 analysis. Patients with low serum NRP-1 demonstrated longer progression free survival when treated with T, at 17.9 months, compared to B, at 11.2 months (HR = 0.380, P= 0.0075). Patients with high serum NRP-1 had progression free survival of 7.3 months and 7.5 months for the T and B arms, respectively. No other biomarker was identified.

Conclusion

The data suggest that NRP1 may have both prognostic and predictive value in mCRC patients treated with angiogenesis inhibitors. Patients with low NRP-1 do better regardless of therapy and may have longer PFS when treated with T rather than B, both in combination with MFOLFOX6. This finding needs to be further validated in a prospective trial of pre-selected patients. The differential activity observed with T vs B, in NRP1 low patients is potentially due to the broader VEGF pathway inhibitory activity of T.